Innovative Method of Alopecia Treatment by Autologous Adipose-Derived SVF

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Kim et al.

Stem Cell Res Ther (2021) 12:486


https://doi.org/10.1186/s13287-021-02557-6

SHORT REPORT Open Access

Innovative method of alopecia treatment


by autologous adipose‑derived SVF
Sun Jong Kim1, Myung Jin Kim1, Young Jun Lee1, Joo Chan Lee1, Ji Hyang Kim2, Do Ha Kim3, Young Hoo Do4,
Jun Woo Choi1, Sung Ill Chung3* and Byung‑Rok Do2*

Abstract
Background: Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes
such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of
the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical
cases to improve AGA through transplantation of autologous SVF into the scalp.
Objective: To confirm the efficacy of the autologous SVF usage to the patients with AGA.
Methods: Nine patients (age range 43–64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffer‑
ing from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp.
Autologous SVF was isolated and characterized prior to the injection of live 7–9 × ­106 cells into the patients’ treatment
site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair den‑
sity 3 and 6 months after post-injection compared to pre-injection status.
Results: Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation com‑
pared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin
on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation
(P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical
significance (P = 0.142 and 0.155, respectively).
Conclusions: One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were
significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of
subjects are satisfied with the result after treatment.
Keywords: Stromal vascular fraction (SVF), Alopecia, Hair loss, Baldness

Introduction grows back, and it can be distinguished clearly from a


Androgenic alopecia (AGA) means the lack of body hair, normal person by withdrawal of the frontal hair line. In
especially follicle of hair, due to various reasons such as case of AGA, there is no special solution with present
endocrine abnormalities, genetic factors, stress, sex and medical technology and although finasteride and minoxi-
age [1, 2]. It is defined as baldness when hair follicle cells dil have been approved by FDA, it merely delays the pro-
are completely destroyed, and it is not likely that the hair gress of AGA and a fundamental treatment has not yet
been reported [3–5].
In general, AGA treatments can be divided into surgi-
*Correspondence: prschung@naver.com; brokdo@hurimbiocell.com cal and non-surgical methods. A representative surgi-
2
Biotechnology Research Institute, Hurim BioCell Inc., Seoul, Korea cal treatment is to transplant hair from the occipital to
3
Top Plastic Surgery, Teheran‑ro 111, Gangnam‑gu, Seoul, Korea the hair loss area which does not make the hair thin or
Full list of author information is available at the end of the article

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Kim et al. Stem Cell Res Ther (2021) 12:486 Page 2 of 9

removed [6–8]. In case of non-surgical treatments, there hair cycle of scalp is also known to be affected by vari-
is no proven method objectively and in order to treat ous environment factors, and the vascularity on the
AGA, it is known to take a 5-red reductase inhibitor scalp may also be an important factor in the health of the
that suppresses production of DHT hormone and if tak- hair root [6–8]. So, it is estimated that improvement of
ing the medicine is stopped, it is estimated that alopecia the condition on the scalp SVF with plenty of stem and
occurred again by reproduction of DHT hormone. AGA vascular cells contributes to restoring hair cycle. In this
is known as a disease in which one’s immune cells gen- study, it is aimed to verify the improvement of alopecia
erate immune inflammatory response to hair roots and by using SVF separated from autologous adipose-derived
become to lose hair in the end. Although various treat- tissues [16–19]. This report is a prospective preliminary
ments have been known to date, it is not known there is study which introduces SVF in the treatment of AGA and
any effective method to inhibit the progression of AGA regarded to be highly utilized in clinical cases which can
by stimulating the scalp itself or to regulate the cycle of suggest a new standard to AGA treatment.
hair which can restore AGA [9, 10].
According to some reports on the efficiency of AGA
improvement using biological formulations such as cul- Materials and methods
ture fluid of platelet-rich plasma (PRP) or adult stem Subjects
cells, the results of the treatment are known to be insig- The medical records of patients were reviewed to collect
nificant. According to a recently published academic patients who treated with autologous SVF for AGA at the
paper, the result of clinical treatment using SVF by lipo- plastic surgery clinic (TOP Plastic Surgery, Seoul, Korea).
suction in patients’ abdomen and thigh has been statis- The medical status and hair loss history were analyzed
tically effective. Treatments applied in the area of AGA through the questionnaire, and a physical experiment was
using adipose-derived stem cells or its culture fluid have conducted to diagnose AGA grade. Healthy adult men
been continuously reported [11]. and women patients between 43 and 64 were enrolled in
Among various clinical studies on mesenchymal stem this study, and androgenic baldness rated recorded using
cells (MSCs), the treatments using SVF from the adi- the Norwood–Hamilton grades and Ludwig scale. Over
pose tissues are reported to be effective on degenerative a period of 6 months, nine patients (4 male and 5 female)
arthritis, treating wound and damaged tissue regen- were followed the results. Table 1 describes the enroll cri-
eration. SVF has been identified through several studies teria for subjects. All subjects had a normal body mass
for the effectiveness of neovascularization stimulation index (BMI) range, generally healthy, and had no history
and inflammatory change reduction, and the stability of underlying disease. Written consent for the portrait
has been reported with several clinical cases [12–14]. rights and publication was taken from all patients, and
SVF includes not only stem cells but also vascular and IRB approved the concerned clinical trial process. Table 2
immune cells, and is known to restore damaged body summarizes patients’ information, including the age, gen-
parts, activating surrounding tissues by secreting vari- der, volume of adipose tissues, isolated SVF and injected
ous cytokines depending on the environment [15]. The SVF cell counts.

Table 1 Subject recruitment criteria in the study

Inclusion Men or women with AGA symptoms


Healthy subjects aged 43–64 years who provide written consent suitable to this study
Subjects with grades II–VI Norwood–Hamilton or Class I–III Ludwig
Subjects with severe hair loss within past 12 months
Subjects who do not have any specific diseases or abnormal health conditions in the interview in relation to AGA​
Subjects with required proper hypodermic fat from the abdominal or thigh without any problem in the process of liposuction
Women who are not pregnant during the test period
Exclusion Subjects with prescription for inflammation, infection, malignancy, allergic diseases, autoimmune diseases, pregnancy, diabetes, anti-throm‑
botic drugs, etc.
Subjects who do not experience any improvement previously in the hair loss treatments, or who have sensitive skin and suffer from the skin
irritation and scratch on the surface of scalp during treatments
Subjects with psychiatric history or other physical illness within 30 days of this clinical trials
Subjects with a history of abnormalities in the blood vessels, heart, lungs, kidneys, digestive organs, liver, central nervous systems, etc., or
who may have a risk of developing these diseases
Women who are during pregnancy or plan on being pregnant throughout the study
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 3 of 9

Table 2 Patient profiles and transplanted SVF information


Subject’s No Age Sex Stage Aspirated adipose Harvested SVF Live SVF Injected live
tissue/cc volume/cc cells × ­106/cc cells × ­106/48
spot

1 51 M Class IV 70.2 15.4 1.62 9.55


2 51 Class IV 90 17.0 1.62 7.68
3 54 Class V 80 17.0 0.65 7.68
4 56 Class V 90 17.0 0.69 7.68
5 43 F Class II 90 14.6 1.01 7.68
6 44 Class II 90 17.0 1.22 7.68
7 48 Class I 90 15.3 1.29 7.68
8 59 Class II 80 17.0 1.32 7,68
9 64 Class III 90 16.0 2.15 7.68
The viability of SVF cells was 95.4 ± 3.6% (range 91.8–99%) before and after needle injection

Liposuction, harvesting, and preparation of adipose tissue Phenotyping SVF

by Attune™ NxT Flow Cytometer (Thermo Fischer Scien-


processing Expression of surface markers on SVF was determined
On the day of surgery, we firstly checked the subjects’
medical conditions regarding lipoaspiration and treat- tific, USA). Using each specific anti-human antibody (BD
ment of SVF. After local anesthesia, tumescent fluid Pharmingen, USA) CD31, CD34, CD45, CD73, CD90,
was infiltrated, and adipose tissue isolated with a 60-mL and CD105 SVF surface marker were used for flow cyto-
clogged syringe from the abdominal subcutaneous layer metric analysis. Isotype control staining was performed
by using a cannula with a diameter 3.0 mm (Medical with IgG1-FITC and IgG2b-PE. Data represent the per-
land, Seoul, Korea). An average 90 cc of adipose tissue centage of positive cells for each marker analyzed on SVF
was extracted from the patients and split into two 50 ml and are means ± SD.
of syringes.
HuriCell System (HC1500, HurimBioCell, Seoul, Treatment of SVF
Korea) was used to obtain SVF according to the man- Without local anesthesia, we disinfect with chlorhex-
ufacturer’s instructions. In general, tissue processing idine on the upper front, biparietal and pyramidal area.
within the HuriCell device uses a sterile disposable set Using a syringe 3 cc (30 gauge), SVF is transplanted into
and the collagenase Type I (Sigma-Aldrich Corp., Seoul. the scalp at 4 mm depth. In advance, 2 cm in a square
Korea). Once the HuriCell disposable kit is placed area (4 sites) to be transplant SVF is marked in the scalp
within the device, the system performs an auto-check and then, 0.15 cc per spot, 48 spots—total 7.2 cc of SVF is
to ensure that it is perfectly sealed. Adipose tissues perpendicularly injected. Without removing immediately
then move into the processing canister and are washed upon after injecting, we stuck the syringe in the scalp for
by warmed saline to decontaminate waste and mixed approx. 2 s to prevent leakage of the injected cells from
blood. HuriCell device calculates the total amount of the transplant site. After treatment, all subjects were pre-
enzyme based on the volume of tissue. The adipose tis- scribed antibiotics for 3 days and recommended not to
sues are continuously agitated in the process of enzy- wash their hair on the day of SVF injection and not to do
matic digestion for 30 min at 37 °C. Once digestion is excessive exercise for approx. 1 week. On the day of the
complete, the SVF fraction is moved to another cham- treatment, all subjects can enjoy their daily lives.
ber, washed further 3 times and centrifuged. After the
process is completed, SVF is resuspended in 15–17 cc Measurements and statistical analysis
of saline and transferred with a syringe. The isolation of We randomized the treated side of the patients, and the
SVF took 75–90 min depending on the amount of adi- improvement was assessed by two independent observ-
pose tissue. We filtered SVF using 70-μm cell strainer ers using Aroma Smart Wizard system (ASW200, Aram
(BD Biosciences, Inc., San Jose, CA, USA) to remove Huvis, Seoul, Korea) without physicians before and after
the aggregated cells. The viability of SVF recovered SVF treatment. After 1, 3 and 6 months, the patients’
from tissue in each patient was determined by a semi- AGA improvement status was confirmed by a physician
automated ADAM MC Cell Counter (NanoEnTek, and AGA standard scores with photographs were taken
Seoul, Korea). by two blinded observers at the same distance each time.
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 4 of 9

Each side for observation symmetrically divided in half we treated 1 mg of finasteride, 0.5 mg of dutasteride for
based on 4 cm from the hairline. Hair density (per ­cm2), men and 3% minoxidil foam for women.
hair thickness, scalp status, keratin of scalp, scalp sen- Table 3 shows the results of the basic phenotype for the
sitivity, scalp sebum, hair pore status, and cuticle status isolated SVF. The transplanted cells which were not puri-
were analyzed automatically by average value measured fied showed a clearly heterogeneous population express-
over at 3 random sites using ASW200. ing not only ADSC markers but also the hematopoietic,
To avoid disturbance by medications administered to immune-related cells and endothelial along with spe-
the patient, all values in these statistics used the differ- cific high levels of CD34 [19]. Compared with the con-
ence of a median value between treated and the non- ventional standard manual purification with HuriCell,
treated sides. Statistical significance was used by the typical SVF characteristics, the viability, and the doubling
Wilcoxon signed-rank test, a nonparametric statistical time were not different significantly (data not shown).
method corresponding to the student’s t test. It was sta- The greatest advantage of isolating SVF by machine is
tistically considered significant if the P values are less the reproducibility of the procedure, thereby reducing
than 0.05. patient-to-patient variability in the isolated cell popula-
tion, which is an important parameter to control when
Results treating with stem cells in the clinic (Tables 4, 5).
Nine patients recruited from November 2020 to May Patients in each group underwent transplantation for
2021 were divided into two parties according to gender: the same quantity of total live SVF (except 1 patient)
male (n = 4) and female (n = 5). We randomly selected according to individual hair loss type. The mean age of
the patient’s treatment side. We managed the isolation patients was 53 ± 1.22 in male group and 51.5 ± 3.43 in
and transplantation of SVF not exceeding 120 min. In female group. A total of 3 patients (30%) had an AGA
accordance with AGA medical prescription guidelines, family history, and the other 6 patients (70%) were
experiencing serious hair loss in the recent past year.
One female (20%) showed Ludwig scale type III, and
three females (60%) did Ludwig scale II. In case of male
Table 3 Phenotyping of cell surface markers on SVF
patients, most of them showed Hamilton–Norwood scale
Marker Percentage of gated Characterization type IV or V. Any side effects were not observed in all
(Means ± SD, n = 3)
subjects.
CD31 33.88 ± 11.45 Endothelial Both groups, the scalp images were taken and the
CD34 55.65 ± 11.85 Hematopoietic number of hair/cm2 was counted randomly in the trans-
CD45 2.33 ± 2.06 Immunological planted area on each visit. In one patient, based on AGA
CD73 12.53 ± 13.39 Mesenchymal condition, we randomly treated a half with SVF, while the
CD90 58.52 ± 11.19 Mesenchymal other part was not done. Mean and median density of
CD105 10.03 ± 8.44 Mesenchymal hair on the pre-injection visit in the non-treated site were
All subjects (n = 3) performed in duplicate experiment, and the number is
44.44 ± 5.09 vs. 43.33 ± 3.11 in the treated site (Fig. 1).
mean ± SEM. The characteristics of isolated cell using HuriCell device show On 6 months after treatment, the number of hair density
similar patterns as published data

Table 4 The change of hair density before and at 1, 3 and 6 months after SVF transplantation
Patient’s no. Age Sex Hair density before Hair density 1 month Hair density 3 months Hair density 6 months
treatment (hair/cm2) (hair/cm2) (hair/cm2) (hair/cm2)
Non-treated Treat Non-treated Treat Non-treated Treat Non-treated Treat

1 51 M 40 50 40 50 55 75 65 90
2 51 30 40 45 50 50 65 65 80
3 54 25 30 40 55 45 75 55 90
4 56 50 45 60 50 60 55 70 85
5 43 F 40 45 40 45 45 70 60 100
6 44 60 55 70 65 75 85 85 95
7 48 55 55 55 60 60 75 70 95
8 59 30 30 35 45 45 65 75 80
9 64 70 40 70 45 55 85 75 95
Average value of hairs was measured automatically over at 3 random sites using Aroma Smart Wizard system (ASW200)
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 5 of 9

Table 5 The change of hair diameter before and at 1, 3 and 6 months after SVF transplantation
Patient’s no. Age Sex Hair thickness before Hair thickness 1 month Hair thickness 3 months Hair thickness
treatment (mm) (mm) (mm) 6 months (mm)
Non-treated Treat Non-treated Treat Non-treated Treat Non-treated Treat

1 51 M 0.022 0.028 0.028 0.031 0.044 0.042 0.047 0.055


2 51 0.028 0.023 0.03 0.023 0.033 0.029 0.047 0.045
3 54 0.018 0.021 0.028 0.029 0.032 0.031 0.049 0.051
4 56 0.029 0.027 0.03 0.033 0.022 0.044 0.033 0.047
5 43 F 0.034 0.028 0.03 0.031 0.04 0.046 0.06 0.063
6 44 0.033 0.035 0.037 0.036 0.038 0.038 0.053 0.056
7 48 0.034 0.025 0.036 0.038 0.048 0.052 0.066 0.082
8 59 0.029 0.038 0.038 0.046 0.04 0.048 0.062 0.063
9 64 0.06 0.038 0.06 0.04 0.061 0.065 0.063 0.068
Average value of the hair diameter was measured automatically over at 3 random sites using Aroma Smart Wizard system (ASW200)

Fig. 1 Analysis of hair density change before and after the Fig. 2 Changes of hair thickness before and after the treatment of
treatment of SVF. The difference of median value between treated SVF. The difference of median value between treated and non-treated
and non-treated side is significantly difference at 3 and 6 months side was increased at 3 and 6 months. However, there was no
(*Wilcoxon signed-rank test, P < 0.05, n = 9) statistical significance (Wilcoxon signed-rank test, n = 9)

was in the non-treated site 68.88 ± 2.97 versus 90 ± 2.35 hair thickness, scalp status, sensitivity, sebum, hair pore
in the treated site. Overall, the density was increased in status, cuticle status, or any other parameters was not
the treated site by 48.11% as compared to the non-treated shown in the treated area at whole 6-month follow-up
site density of 35.48%. Hair density of the treated side was except hair density and keratin of scalp (Fig. 3). Although
highly improved after 3- (P = 0.01, n = 9) and 6-month the patients do not achieve any improved scores in their
pre-injection (P = 0.009, n = 9) (Fig. 1). hair status, significant improvement in the score for the
Hair thickness improvement was observed after 3 and 6 keratin of the hair epidermis was seen in the treated side
months post-injection, but there was no statistical signifi- as compared to the non-treated side (P = 0.032). After
cance (Fig. 2). The mean and median thickness of hair on 6 months, most of the patients showed improvement in
the pre-injection visit were 0.032 ± 0.053 mm in the des- the hair status and patient satisfaction scores (data not
ignated non-treated site compared to 0.029 ± 0.003 mm shown). Also, the pull test was done in both sides of the
in the designated treated site. On the 6 months post- patients after 6 months, and there is no significance com-
injection visit, hair thickness was 0.053 ± 0.003 mm in pared to non-treated group (data not shown). Represent-
the non-treated site compared to 0.058 ± 0.003 mm in ative photographs and macrophotographs of a patient
the treated site. Any overall significant change in the after 6 months are shown in Fig. 4.
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 6 of 9

autologous MSCs [10, 11] for AGA treatment, and it has


been reported that AGA improvement using SVF is more
effective and discovery of cell secretion for the cell death/
necroptosis regarding hair follicle will be a breakthrough
to AGA [21]. But it is necessary that careful design of
microenvironment to activate SVF, development of cell
transplantation protocols to maximize the capabilities of
SVF while preventing unexpected cell behavior and the
proper selection of target diseases will be also a critical
factor to lead successful clinical applications.
In this study, the therapeutic role of SVF was assessed
by AGA-related criteria such as hair density, thickness,
and other status of scalp. The median hair density on
the treated side was significantly increased compared
to the non-treated side (P = 0.009 and 0.032, respec-
tively). However, although increase in the thickness was
observed at 3 and 6 months post-injection, there was no
statistical significance (P = 0.142 and 0.155, respectively).
This result is thought to be related to the thickness of
newly generated hair and so it is necessary to extend
the observation period. In relation to the status of scalp,
functionless hair follicles full of hyperkeratotic plugs [22],
assumed incapable of making new hair grow, showed
more significant improvement in the score for the keratin
of the scalp in the treated side as compared to the non-
treated side (P = 0.032).
Fig. 3 Representative image of keratin on scalp pre-injection and So far, one of representative AGA treatments is to use
6 months after SVF treatment. The median value between treatment anti-androgen drugs which suppresses male hormone
and non-treatment side was significantly different at 6 month
(Wilcoxon signed-rank test, *P < 0.05). 51-year-old men (A, B) and
and the other one is to use minoxidil. In addition, new
43-year-old woman (C, D) decreased the score of keratin on scalp anti-androgen drugs and medical devices are currently
after 6 months post-injection being developed and hair follicle regeneration research
using some follicle cells is ongoing. Among these treat-
ments, it is known that it is difficult to do long-term
Discussion use for anti-androgen drugs, due to the side effects of
This study investigated the potential role on the SVF on inhibiting male hormone. In case of minoxidil, hair loss
AGA. Similar to MSCs, SVF is available in large quanti- inhibition is not appeared to all patients and there is dis-
ties from the abdomen or thigh in a relatively less inva- satisfaction with sense of use. Other technologies such
sive liposuction, which is considered as a useful tool for as hair follicle transplantation and medical devices have
the cell-based treatment, just like bone marrow-derived been developed, but there are some limitations such as
stem cells. SVF consists of ASCs, endothelial cells, peri- cost burden and somewhat weak effectiveness [22–26].
cytes, macrophages and other immune-related cells The results of this study show that approx. 48% of the
which secrets neovascular factors responding to ischemia hair density has been improved after the transplantation
or stimulates growth factor. Due to these characteristics of autologous SVF. The improved effect of the hair loss
of SVF, stem cells using minimal manipulation have been using autologous SVF can be a good treatment model for
a very active topic in many studies and so, the concerned men as well as women. Furthermore, the improvement of
clinical studies on SVF have been highly popular [14]. hair loss using SVF is considered to have a good, expected
Recently, improvement of AGA treatment with SVF effect on AGA when used in combination with existing
has been used as an effective method in the various biological treatment methods such as follicle stem cells
translational researches. Using cultured or uncultured therapy [27]. Though previous study for animal mod-
SVF [17], regeneration, immune control and angiogen- els on hair growth has been published, there are not so
esis promotion and its corresponding utility have been many cases in clinical trials to improve or inhibit AGA
spread in the clinics in the easiest and most promising using SVF [28]. In the recent examples when minoxidil,
way [19, 20]. Recently, there are studies using PRP or an AGA treatment agent is used in combination with
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 7 of 9

Pre-injection At 6 months Pre-injection At 6 months

1 6

2 7

3 8

4 9

Fig. 4 Representative photographs of the AGA improvement after SVF treatment. Baseline (pre-injection) versus 6 months (post-injection) global
photographs after treatment

autologous SVF transplantation, and it has been reported In the application of clinical study using SVF, the type,
that hair growth is improved, which is known as parac- structure, and surroundings of damaged tissue/organ
rine effect by the migration of transplanted SVF and the have an important influence on the transplanted SVF
secretion of various growth factors [29]. As it is known, [31, 32]. Efficacy on SVF-based therapy in AGA depends
SVF secrets various cytokines related to immunosup- on several variables such as optimal cell number, pheno-
pressive action or anti-inflammation by interaction of type, maturity formulation and transplantation method.
various cells [30]. Like other stem cells, the fate of transplanted SVF is
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 8 of 9

determined by various microenvironments such as apop- Availability of data and materials


All concerned data or analysis included in this study are available in the article.
tosis, extracellular material decay, bleeding, inflamma-
tion, hypoxic environment, cytokine, tissue damage,
mechanical strength, and other factors. Furthermore, Declarations
it is necessary to study the role of numerous cells, the Ethics approval and consent to participate
preparation process, intercellular interactions, extracel- The study was conducted according to the criteria of the Declaration of
Helsinki and registered in https://​cris.​nih.​go.​kr/ (Identifier: KCT0005880) and
lular substrates, growth factors and biomaterials, "on/off" performed retrospectively. This clinical study was approved by the Institutional
signaling pathways, and the microcellular environment Review Board of Korea National Institute for Bioethics Policy (KNIFBP). After
acting at each stage of tissue/organogenesis [33]. obtaining written consent for all enrolled subjects, Dr. Sung Ill Chung (plastic
surgeon) of Top Plastic Surgery Hospital (Gangnam-gu, Seoul, Korea) isolated
This study did not complete blind process for subjects and transplanted SVF. The first patient was enrolled in November 2020.
and has a limitation for a small number of subjects to
recruit. Despite these limitations, this study presented Consent for publication
Written consent was obtained for the subject’s personal clinical information or
fundamental improvement of AGA using autologous SVF photographs to be used in the journal. Consent form to this can be provided
and in the future, progressive study is required to be car- for review by journal.
ried out by improving research design.
Competing interests
This strategy can suggest not only a treatment itself for All authors who participated in this study agree they do not have any interests
AGA but also be helpful to develop regenerative medi- to conflict each other. The authors belonging to HurimBioCell supported only
cine applications successfully. But, to overcome the limi- operation of Huricell device, while the data from the clinical trials were fully
calculated and analyzed by Top Plastic Surgery. Accordingly, there is no mutual
tations in this study, AGA treatments with various causes interest between two parties regarding the issue on this paper.
and complex mechanism, therapeutic agent development
for AGA is considered to be essential. As the underly- Author details
1
Department of Bioconvergence, HurimBioCell Inc., Seoul, Korea. 2 Biotechnol‑
ing cause of AGA is prevented by SVF, if the long-term ogy Research Institute, Hurim BioCell Inc., Seoul, Korea. 3 Top Plastic Surgery,
safety and efficacy are secured, compared to conventional Teheran‑ro 111, Gangnam‑gu, Seoul, Korea. 4 Department of Applied Statistics,
treatment method, it is expected to provide an effective College of Natural Science, Hanyang University, Seoul, Korea.
method to cure AGA in the future. Received: 19 May 2021 Accepted: 26 July 2021

Conclusions
This study using autologous SVF can be regarded as a cell
therapy method to differentiate from existing AGA treat- References
ments. This study proved to improve and maintain hair 1. Hamilton JB. Patterned loss of hair in man: types and incidence. Ann N Y
density for more than 6 months through single injection Acad Sci. 1951;53:708–28.
2. Norwood O. Male pattern baldness: classification and incidence. South
of SVF and verified the improvement of some criteria Med J. 1975;68:1359–65.
on the effect of AGA inhibition. In the future, additional 3. Otberg N, Finner AM, Shapiro J. Androgenetic alopecia. Endocrinol Metab
studies on more suitable transplant methods using SVF Clin N Am. 2007;36:379–98.
4. Stough D, Stenn K, Haber R, et al. Psychological effect, pathophysiol‑
and establishment of clinical treatment protocols for ogy, and management of and rogenetic alopecia in men. May Clin Proc.
improving effects on AGA will be also required to be 2005;80:1316–22.
done. 5. Krupa Shankar DS, Chakravarthi M, Shilpakar R. Male androgenetic alope‑
cia: population base study in 1,005 subjects. Int J Tricol. 2009;1:131–3.
6. Perez-Meza D, Niedbalski R. Complications in hair restoration surgery. Oral
Maxillofac Surg Clin N Am. 2009;21:119–48.
Abbreviations 7. Blumeyer A, Tosti A, Messenger A, et al. Evidence-based (S3) guideline for
ADSCs: Adipose-derived stem cells; MSCs: Mesenchymal stem cells; AGA​ the treatment of and rogenetic alopecia in women and in men. J Dtsch
: Androgenetic alopecia; SVF: Stromal Vascular fraction; PRP: Platelet-rich Dermatol Ges. 2011;9:1–57.
plasma. 8. Rossi A, Anzalone A, Fortuna MC, et al. Multi-therapies in androgenetic
alopecia: review and clinical experiences. Dermatol Ther. 2016;29:424–32.
Acknowledgements 9. Van Dongen JA, Stevens HP, Harmsen MC, van der Lei B. Mechanical
We would like to thank all authors who contributed to the paper and all micronization of lipoaspirates: squeeze and emulsification techniques.
relationships. Plast Reconstr Surg. 2017;139:1369–70.
10. Zhu M, Zhou Z, Chen Y, et al. Supplementation of fat grafts with adipose-
Authors’ contribution derived regenerative cells improves long-term graft retention. Ann Plast
SJK, SIC and BRD contributed to study concept, design, and conduction to Surg. 2010;64:222–8.
this study. MJK, YJL and JHK contributed to operation of HuriCell and data col‑ 11. Hieronymus PS, Simone D, Julia DB. Introducing platelet-rich stroma:
lection. YHD contributed to statistical data analysis. JCL contributed to manu‑ platelet- rich plasma (PRP) and stromal vascular fraction (SVF) com‑
script writing and editing. DHK, JWC and SIC contributed to patient selection bined for the treatment of androgenetic alopecia. Aesthet Surg J.
and procurement. All participating authors approved the final manuscript. 2018;13:811–22.
12. Chu DT, Nguyen TPT, Tien NLB, et al. Adipose tissue stem cells for therapy:
Funding an update on the progress of isolation, culture, storage, and clinical
HurimBioCell supported SVF isolation kit for research Grant (HBC202104). The application. J Clin Med. 2019;8:917.
other works in this article received no external funding.
Kim et al. Stem Cell Res Ther (2021) 12:486 Page 9 of 9

13. Mizuno H, Tobita M, Uysal AC. Concise review: adipose-derived stem treatment of androgenetic alopecia in men. J Am Acad Dermatol.
cells as a novel tool for future regenerative medicine. Stem Cells. 2002;47:377–85.
2012;30:804–10. 25. Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized, placebo-con‑
14. Gentile P, Scioli MG, Bielli A, Orlandi A, Cervelli V. Concise review: the use trolled trial of 5% and 2% topical minoxidil solutions in the treatment of
of adipose-derived stromal vascular fraction cells and platelet rich plasma female pattern hair loss. J Am Acad Dermatol. 2004;50:541–53.
in regenerative plastic surgery. Stem Cells. 2017;35:117–34. 26. Fertig RM, Gamret AC, Darwin E, et al. Sexual side effects of 5-α-reductase
15. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Self-renewal, multi‑ inhibitors finasteride and dutasteride: a comprehensive review. Dermatol
potency, and the existence of two cell populations within an epithelial Online J. 2017;23:3.
stem cell niche. Cell. 2004;118:635–48. 27. Goren A, Naccarato T. Minoxidil in the treatment of androgenetic alope‑
16. Shin H, Won CH, Chung WK, et al. Up-to-date clinical trials of hair regen‑ cia. Dermatol Ther. 2018;31:e12686.
eration using conditioned media of adipose-derived stem cells in male 28. David PM, Craig Z, Marcos S, Ganesh K, Edward B, Eric D. Hair follicle
and female pattern hair loss. Curr Stem Cell Res Ther. 2017;12:524–30. growth by stromal vascular fraction enhanced adipose transplantation in
17. Narita K, Fukuoka Sekiyama H, Suga H, Harii K. Sequential scalp assess‑ baldness. Stem Cells Cloning. 2017;6(10):1–10.
ment in hair regeneration therapy using an adipose-derived stem cell- 29. Ghazal B, Ijaz H, Fridoon JA, Mahmood SC. Stromal vascular fraction-
conditioned medium. Dermatol Surg. 2020;46:819–25. enriched platelet-rich plasma therapy reverses the effects of androge‑
18. Kilroy GE, Foster SJ, Wu X, Ruiz J, et al. Cytokine profile of human adipose- netic alopecia. J Cosmet Dermatol. 2020;19:1078–85.
derived stem cells: expression of angiogenic, hematopoietic, and pro- 30. Kubanov AA, Gallyamova YA, Korableva OA. The study of growth
inflammatory factors. J Cell Physiol. 2007;212:702–9. factors in patients with androgenic alopecia. J Biomed Pharmacol.
19. Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose 2017;10:1219–28.
tissue derived stromal vascular fraction and culture expanded adipose 31. Young JT, Sang YL, Cho AR, Kim YS. A randomized, double-blind, vehicle-
tissuederived stromal/stem cells: a joint statement of the International controlled clinical study of hair regeneration using adipose-derived stem
Federation for Adipose Therapeutics and Science (IFATS) and the Interna‑ cell constituent extract in androgenetic alopecia. Stem Cells Transl Med.
tional Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15(6):641–8. 2020;18:1–11.
https://​doi.​org/​10.​1016/j.​jcyt.​2013.​02.​006. 32. Fukuoka H, Suga H. Hair regeneration treatment using adipose-derived
20. Ramdasi S, Tiwari SK. Growth factors and cytokines secreted in condi‑ stem cell conditioned medium: follow-up with trichograms. Eplasty.
tioned media by mesenchymal stem cells-promising possible therapeutic 2015;15:e10.
approach for hair regeneration. J Stem Cells. 2016;11:201–11. 33. Gentile P. Autologous cellular method using micrografts of human
21. Ibrahim ZA, Elmaadawi IH, Mohamed BM, et al. Stem cell therapy as a adipose tissue derived follicle stem cells in androgenic alopecia. Int J Mol
novel therapeutic intervention for resistant cases of alopecia areata and Sci. 2019;20:e3446.
androgenetic alopecia. J Dermatol Treat. 2016;24:1–10.
22. Tinoco A, Gonçalves J, Silva C, Loureiro A, Gomes AC, Cavaco-Paulo A,
Ribeiro A. Keratin-based particles for protection and restoration of hair Publisher’s Note
properties. Int J Cosmet Sci. 2018;40:408–19. Springer Nature remains neutral with regard to jurisdictional claims in pub‑
23. Kelly Y, Blanco A, Tosti A. Androgenetic alopecia: an update of treatment lished maps and institutional affiliations.
options. Drugs. 2016;76:1349–64.
24. Olsen EA, Dunlap FE, Funicella T, et al. A randomized clinical trial of
5% topical minoxidil versus 2% topical minoxidil and placebo in the

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